This document summarizes various drugs used for the chemotherapy of protozoal infections. It discusses drugs used to treat amebiasis, giardiasis, trichomoniasis, and other protozoal infections. The main drugs covered are metronidazole, tinidazole, diloxanide furoate, emetine, dehydroemetine, chloroquine, nitazoxanide, and 8-hydroxyquinolines. It provides details on the mechanisms of action, uses, pharmacokinetics, and adverse effects of these anti-protozoal drugs.

1. CHEMOTHERAPY OF
PROTOZOAL INFECTIONS
1

2. PROTOZOAL INFECTIONS
MALARIA
AMEBIASIS
GIARDIASIS
TRICHOMONIASIS
TRYPANOSOMIASIS
LEISHMANIASIS
TOXOPLASMOSIS
BABESIOSIS
BALANTIDIASIS
OTHER PROTOZOAL INFECTIONS 2

3. AMEBIASIS
3

4. DEFINITION: AMEBIASIS is infection with the parasitic
intestinal protozoan ENTAMOEBA HISTOLYTICA( the
“tissue-lysing amoeba)
4

5. AMEBIASIS- A MAJOR HEALTH
PROBLEM
10% World Population
50 million people with Invasive disease
Death in 1,00,000 of these annually
Third most common cause of death from parasitic
disease after Malaria and Schistosomiasis
More commonly seen where poor sanitation and
crowding compromises barriers to contamination of
drinking water and food with feces
5

6. MODES OF TRANSMISSION
Fecal contamination of
drinking water and
foods, but also by
direct contact with dirty
hands or objects as
well as by sexual
contact.
Additionally, geophagy
is a common route of
infection in certain
cultures.
6

7. SEVERAL FACTORS CONTRIBUTE TO
INFECTION
HOST FACTORS
Stress
Malnutrition
Alcoholism
Corticosteroid therapy
Immunodeficiency
Alteration of bacterial flora
RISK FACTORS
People in developing
countries that have poor
sanitary conditions
Immigrants from developing
countries
Travellers to developing
countries
HIV-positive patients
Men who have sex with men
7

8. LIFE CYCLE
Infective form
Can survive outside
the human body
Transform to
trophozoites
Non infective(invasive)
Can reproduce
feed on intestinal bacteria
or invade and ulcerate
wall of large intestine, &
may migrate to liver or
other tissues
Transform to cysts which
are excreted in feces 8
CYST TROPHOZOITE

9. LIFE CYCLE
9

10. CLASSIFICATION OF ANTIAMOEBIC
DRUGS
TISSUE AMOEBICIDES
INTESTINAL AND EXTRA
INTESTINAL AMOEBICIDES
 NITROIMIDAZOLES
METRONIDAZOLE,
TINIDAZOLE, ORNIDAZOLE,
SECNIDAZOLE,
SATRANIDAZOLE
 ALKALOIDS
EMETINE, DIHYDROEMETINE
EXTRA-INTESTINAL
AMOEBICIDES
 CHLOROQUINE
LUMINAL AMOEBICIDE
AMIDES
 DILOXANIDE FUROATE,
NITAZOXAMIDE
8-HYDROXYQUINOLINE
 QUINODOCHLOR
(IODOCHLOROHYDROXYQU
IN,CLIOQUINOL),
DIIODOHYDROXYQUIN
(IODOQUINOL)
ANTIBIOTICS
 TETRACYCLINES,
PAROMOMYCIN
10

11. METRONIDAZOLE- PROTOTYPE
Originally discovered and used for Trichomoniasis in 1959
1-(β-Hydroxyethyl)-2-Methyl-5-Nitroimidazole
Nitro group
on C5
essential for
its activity
11

12. ANTIMICROBIAL SPECTRUM
Broad spectrum cidal activity against Anaerobic Protozoa
 E. histolytica
 T. vaginalis
 G. lamblia
Anaerobic bacteria – B.fragilis, Cl.perfringes, H.pylori, Cl.
Difficile, Fusobacterium, Camplyobacter, Peptococci,
Spirochetes & Anaerobic Streptococci
Extraction of adult guinea worm(Drancunculia medinensis)
Resistance – No significant resistance for E. histolytica till
now, but developed for T. vaginalis
12

13. MECHANISM OF ACTION
Selective toxicity to Anaerobic & Microaerophilic
microorganisms
A system unique to anaerobics - Pyruvate:ferredoxin
oxidoreductase pathway (PFOR) normally generates
ATP via oxidative decarboxylation of pyruvate
13

14. Entry into the microorganism by
diffusion
Nitro group is reduced by redox
proteins to highly reactive nitro
radical
Nitro radicals act as an electron sink
Competes with Biological acceptor
sites of anaerobic organisms for the
electrons generated by PFOR
pathway of pyruvate reduction 14

15. METRONIDAZOLE In Addition,
3 CAUSE
RADIOSENSITIZATION
2
1 INHIBITS CELL
MEDIATED IMMUNITY
INDUCE
MUTAGENESIS
15

16. PHARMACOKINETICS
ABSORPTION
Vd ~ total
body
water
<20%
bound to
plasma
protein
t1/2- 8 hrs
Completely
absorbed from
small intestine,
little amount
reaches colon
16

17. THERAPEUTIC USES
1. AMEBIASIS
First line drug among all forms of amoebic infection
Current recommendations
• 800mg TDS for 7-10 days
INVASIVE DYSENTRY & LIVER ABSCESS
• 500mg iv infusion 6-8hrly for 7-10days or till oral therapy
can be started
SEVERE CASES OF AMEBIC DYSENTRY &
LIVER ABSCESS
• 400 mg TDS for 5-7 days
MILD INTESTINAL DISEASE
17

18. 2. GIARDIASIS
 Highly effective in a dose 400 mg TDS for 7 days
 Shorter course of 3 days with 2g/day- equally effective
3.TRICHOMONAS VAGINALIS
 Drug of Choice: 2 g Single dose preferred
18

19. 4. ANAEROBIC BACTERIAL INFCETIONS
 Occurs mostly after Colorectal or pelvic surgery,
appendicectomy
 Brain abscess & endocarditis may be caused by anaerobic
organisms
 Metronidazole in Combination with Gentamycin or
Cephalosporins- Effective
 Severe Cases i.v. administration recommended
 Prohylactic Use in high risk situations(Colorectal/Biliary Sx)
Other drugs used in
anaerobic infections-
Clindamycin &
Chloramphenicol
19

20. 5. PSEUDOMEMBRANOUS ENTEROCOLITIS
 400-800 mg BD-TDS for 10-14 days more effective, more
convenient, less toxic & preferred over Vancomycin
6. HELICOBACTER PYLORI GASTRITIS/PEPTIC ULCER
Metronidazole
400mg TDS or
Tinidazole 500
mg BD
Amoxicillin/
Clarithromycin
Proton pump
inhibitor
Triple drug for 2 week regimens
20

21. 7. ACUTE NECROTIZING ULCERATIVE GINGIVITIS(ANUG)
 Also k/a TRENCH MOUTH caused by anaerobes like
fusobacteria, spirochetes & bacteroides
 Metronidazole/Tinidazole Drug of Choice
21

22. 8. GUINEA WORM INFESTATION
Niridazole- Drug of choice, but unavailable in India
DOSE: 200-400 mg TDS for 7 days
Local reaction suppressed
Anti-inflammatory action
Extraction facilitated
Metronidazole
22

23. ADVERSE DRUG REACTIONS
Most common - Anorexia, Nausea, Vomiting, abdominal
cramps and metallic taste
Less frequent – headache, glositis, rashes, dryness of mouth,
dizziness & loose stools
Urticaria, flushing, itching, rashes & fixed drug eruption
occurs in allergic subjects, warrants discontinuation &
precludes further use
Prolonged administration – Peripheral neuropathy and
CNS effect
Seizures at high doses
Leucopenia, likely with repeated courses 23

24. CONTRA-INDICATIONS
First trimester of pregnancy due to its mutagenic
potential
Neurological diseases and Blood dyscrasias
Chronic alcoholism
Disulfiram-like intolerance to alcohol occurs in some
patients taking Metronidazole
 Symptoms: flushing, burning sensation, throbbing
headache, perspiration, dizziness, vomiting, visual
disturbance, mental confusion, fainting and circulatory
collapse
24

25. TINIDAZOLE
Suited for Single dose or Once daily therapy
Metabolism slower, t1/2- 12 hr, longer duration of
action
Higher cure rates
Better tolerated
Lower incidence of side effects: Nausea(1%),
Rash 0.2(%), Metallic taste (2%)
25

26. THERAPEUTIC USE
INTESTINAL AMEBIASIS
AMEBIC LIVER ABSCESS
TRICHOMONIASIS & GIARDIASIS
H.pylori
ANAEROBIC INFECTIONS
26

27. SECNIDAZOLE
• Congener of
Metronidazole with
similar spectrum of
activity & potency
• Rapid & complete
oral absorption
• Slower metabolism
• t1/2: 17-29 hrs
• Single 2 g dose
high cure rate
• Side effect similar
to Metronidazole
with incidence of
2-10%
ORNIDAZOLE
• Similar activity to
Tinidazole
• Slower metabolism
• Longer t1/2:12-14
hrs
• Dose & duration of
regimen similar to
Tinidazole
• Side effects similar
to Tinidazole
SATRANIDAZOLE
• Longer t1/2: 14 hrs
• Better tolerated
• No nausea,
vomiting or
metallic taste
• Absence of
Neurological &
Disulfiram-like
reactions
• Doesn’t produce
acetabolite
metabolite, which
is weak
carcinogen
27

28. ALKALOIDS
EMETINE
DEHYDROEMETNE
CHLOROQUINE
28

29. EMETINE AND DEHYDROEMETNE
CHEMISTRY
 Emetine hydrochloride, plant alkaloid
derived from Cephaelis ipecacuanha
 Dehydroemetine, Synthetic Analogue
29

30. MECHANISM OF ACTION
Inhibits
elongation of peptide chain
Inhibits Protein synthesis
Inhibits intraribosomal translocation of
tRNA-amino acid complex
1
3
2
Effective
against
trophozoites
only
Potent,
rapid
action
but not
curative
30

31. USES
Amebic liver abscess
Intestinal wall infections
Severe forms of amebiasis, Acute Amebic Dysentery
dehydroemetine is preferable as its less toxic to heart & less
cummulative
Seldom used now only for patients not responding to
metronidazole
Luminal amoebicide must be followed to eradicate cyst
forming trophozoites
31

32. ADVERSE DRUG REACTIONS
Local irritant: pain, tenderness & even abscess formation
at site of injection is most common
Gastrointestinal tract discomfort:
 Nausea, Vomiting, Diarrhoea due to CTZ stimulation &
gastric irritation- Most frequent
 abdominal cramps
Neuromuscular blockade: muscle weakness & muscle
stiffness
Cardiac toxicity: Arrhythmias, Hypotension, Tachycardia,
Myocarditis & ECG Changes
Not be used in patients with cardiac or renal disease, in
children, or in pregnancy
32

33. CHLOROQUINE
Kills trophozoites of E. histolytica
Highly concentrated in liver – used in Hepatic Amoebiasis
Completely absorbed from upper intestine – not effective in
invasive dysentery or luminal cycle
Efficacy in amoebic liver abscess is equal to emetine, but
has longer duration of treatment & frequent relapse
Used after a course of Metronidazole – but a luminal
amoebicide must be added
33

34. DILOXANIDE FUROATE
Highly effective luminal amoebicide
Kills trophozoites responsible for production of cysts –
however no antibacterial action
Diloxanide
Furoate
Diloxanide Furoic acid
80-90% of free diloxanide
absorbed
No systemic effects
10-20% not absorbed,
real antiamoebic
substance
Hydrolysed
34

35. Metabolised by Glucurinadtion & Excreted in urine
USES
Single course produce high cure rate(90%): Mild intestinal
amoebiasis/ Asymptomatic cyst passers
Tissue amoebiasis & Liver abscess with Metronidazole
Chronic cyst passers require repeat course for Eradication
Dose: 500mg TDS for 5-10 days
ADRs: Well tolerated, flatulence, nausea, itching & rarely
urticaria 35

36. NITAZOXANIDE
Salicylamide congener of Antihelminthic Niclosamide
introduced for treatment of Giardiasis & Cryptosporidiosis
SPECTRUM
 G.lamblia
 Cryptosporidium parvum
 Also Effective against E. Histolytica, T. Vaginalis, H. Pylori,
Ascaris
P/Ks
 Prodrug converted to Tizoxanide after absorption
 Glucuronide conjugated & excreted in Urine & Bile 36

37. MOA
Tizoxanide, Inhibitor of PFOR enzyme (essential for electron
transport energy metabolism in Anaerobic organisms)
USES
 Giardiasis, Amoebic Dysentery as luminal amoebicide
 Most effective for Cryptosporidium infection(88%) causing
Diarrhoea in Children & AIDS patients
ADRs
Mild & infrequent - Abdominal pain, vomiting & headache
Dose: 500 mg BD for 3 days 37

38. 8-HYDROXYQUINOLONES
SPECTRUM
Active against Entamoeba, Giardia, Trichomonas, some
fungi (Dermatophytes & Candida) & Bacteria
QUINODOCHLOR
(IODOCHLOROHYDROXY
QUIN, CLIOQUINOL),
DIIODOHYDROXYQUIN
(IODOQUINOL)
38

39. 8-HYDROXYQUINOLONES
 USES
 Alternative to DF in intestinal amebiasis(cheap & good acceptability)
 Giardia, local treatment of Monilial & Trichomonas Vaginitis, Fungal and
bacterial infections
 ADRs Once a popular drug – but less now because of ADRs
 Well tolerated – only Nausea, transient loose & green stools & pruritus but
if used improperly has toxic potential
 Iodism (furunculosis & inflammation of mucous membrane) Goiter may
develop
• Those sensitive- Acute reaction with fever, chills, angioedema &
cutaneous haemorrhages 39

40. With prolonged/repeated use of relatively high doses caused
a Neuropathic syndrome k/a Subacute myelo-optic
neuropathy (SMON)
inflammation of the optic nerve
complete or partial loss of vision & peripheral neuropathy
 In India, prohibited for pediatric use( use for chronic
diarrhoeas caused blindness)
 Fixed dose combination except for external application
banned in India
 Caution note is inserted that use of high dose for more than
14 days, may cause Neuritis & Optic damage 40

41. ANTIBIOTICS- TETRACYCLINE
MOA: Direct inhibitory action on Entamoeba
41
Older tetracyclines absorbed
incompletely
Larger amount reaches Colon
Inhibits bacterial flora with which
Entamoeba lives symbiotically
Indirectly reduces proliferation of
Entamoeba

42. USES
 Chronic case in conjunction with more effacious luminal
amoebicide
 Management of Amoebic dysentry: Added as third drug
in combination with Nitroimidazole & a luminal
Amoebicide
42

43. PAROMOMYCIN
Aminoglycoside resembles Neomycin
SPECTRUM
 E. Histolytica, G.lamblia, Cryptosporidium parvum, T.
Vaginalis, Leishmania & some tape worm
 Antibacterial Spectrum similar to Neomycin
43

44. MECHANISM OF ACTION
Binding to 30S ribosome inters with Protein synthesis
Efficacious luminal amoebicide
P/KS
Orally administered- acts in gut lumen only
Neither absorbed nor degraded
Eliminated unchanged in faeces
44
FREE
FROM
SYTEMIC
TOXICITY

45. USE
 Asymptomatic cyst passer & Chronic Amebic colitis
 Along with Metronidazole in Acute Amebic Dysentry as well
as in Hepatic Amebiasis to eradicate luminal cycle
 Alternative drug for Giardiasis especially during 1st trimester
of pregnancy when Metronidazole & other drugs are
contraindicated
 Cryptosporidiosis, efficacy uncertain
 Trichomonas Vaginitis & Derma Leishmaniasis- used topically
SIDE EFFECTS: Nausea, Vomitting, Abdominal cramps,
Diarrhoea, rarely Rashes 45

46. 46